Quality of life after gastric sleeve and gastric bypass for morbid obesity.
Quality-of-life measures improve as early as 3 months after bariatric surgery.There is wide variability in reporting that renders direct comparisons difficult.The available comparisons between RYGB and sleeve gastrectomy could not detect any difference.Improvement in PRO measures might be related to weight loss.Larger and better designed studies are required to achieve discrimination in PRO measures. Obesity is associated with reduced quality-of-life (QoL), which generally improves after bariatric surgery. The differential effect of each type of surgery (gastric sleeve [SG] and gastric bypass [RYGB]) on QoL is not yet fully understood. To understand which of these surgeries offers greatest improvement in QoL and patient satisfaction. Systematic literature search on Pubmed in July 2014. Relevant articles were selected in a step-wise approach. The 2482 titles were scanned for relevance and 191 were selected for abstract reviewing; and 88 papers were selected for full text analysis. Only 5 papers compared the 2 techniques and only 17 more had retrievable data either on SG or RYGB. The reports were very heterogeneous, preventing a direct comparison of patient reported outcomes (PRO) among studies.Improved results have been reported as early has 3 months and SF-36 scores were improved in all domains in medium to long-term. The question remains whether the improvement in QoL is related to the weight loss and which factors are associated with improved patients' perceptions. There is wide heterogeneity in the reporting of PRO measures after bariatric surgery, but data is consistent with a significant improvement after both surgeries.Larger and better-designed studies are required to understand if there are significant differences in the quality of life after SG or RYGB.


Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and histopathologic correlation.
Degenerative disc disease is a major source of disability in humans. The baboon model is an excellent natural disease model to study comparable human disease, because baboons are relatively large (adult males 20-26 kg, adult females 12-17 kg), long-lived (30-45 years), well defined, easy to use, and closely related to humans. Published investigations with plain radiographs of disc degeneration in baboons indicated vertebral anatomy and changes that were remarkably similar to those seen in humans, and it would be valuable to determine if magnetic resonance imaging (MRI) and histopathologic evaluation would be useful methods for studying the model, as MRI allows multi-planar visualization of tissues without the use of intravenous contrast and it is superior for evaluating disc hydration, annulus tears, and herniations. The thoracolumbar junctions from 47 randomly selected baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and histopathology. Excellent correlation with MRI was observed for changes in disc desiccation, height, and age (P < 0.001). The pathologic analysis demonstrated P values of < 0.001 when comparing histopathology with age and MRI results. All severely degenerated discs seen by MRI were in baboons 14 years of age or older.


Combinatorial Effect of Temozolomide and Naringenin in Human Glioblastoma Multiforme Cell Lines.
Glioblastoma multiforme (GBM) is a grade IV, lethal, and the most common type of brain tumor. GBM can acquire resistance to temozolomide (TMZ) recommended for its treatment. Naringenin (NAG), a flavonoid generally found in grapefruit, has antioxidant, anti-proliferative, and anti-inflammatory properties. It has been reported that phytochemicals can reduce resistance and improve the efficacy of a chemo-resistant drug. The combinatorial effect of TMZ and NAG on cell proliferation was evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay, and the apoptosis in the U87MG and LN229 GBM cells were evaluated by change in fluorescence intensity. The effect of NAG and TMZ on anchorage-independent single-cell colony formation and cell migration was investigated. NAG and TMZ demonstrated enhanced cytotoxic effects on U87MG and LN229 cell lines. The combination index value being less than one indicated the synergistic action of the two drugs in restricting the growth of the cells. The NAG and TMZ together resulted in higher fluorescence intensity as compared to the alone drug. Further, the study showed a marked reduction in the migration of the cells and the formation of a single cell colony.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1952438.


Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation.
Recent studies have demonstrated that the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10), the antagonist of the phosphosphoinositol-3-kinase (PI3K) signaling cascade, is susceptible to H2O2-dependent oxidative inactivation. This study describes the use of redox-engineered cell lines to identify PTEN as sensitive to oxidative inactivation by mitochondrial H2O2. Increases in the steady state production of mitochondrial derived H2O2, as a result of manganese superoxide dismutase (Sod2) overexpression, led to PTEN oxidation that was reversed by the coexpression of the H2O2-detoxifying enzyme catalase. The accumulation of an oxidized inactive fraction of PTEN favored the formation of phosphatidylinositol 3,4,5-triphosphate at the plasma membrane, resulting in increased activation of Akt and modulation of its downstream targets. PTEN oxidation in response to mitochondrial H2O2 enhanced PI3K signaling, leading to increased expression of the key regulator of angiogenesis, vascular endothelial growth factor. Overexpression of PTEN prevented the H2O2-dependent increase in vascular endothelial growth factor promoter activity and immunoreactive protein, whereas a mutant PTEN (G129R), lacking phosphatase activity, did not. Furthermore, mitochondrial generation of H2O2 by Sod2 promoted endothelial cell sprouting in a three-dimensional in vitro angiogenesis assay that was attenuated by catalase coexpression or the PI3K inhibitor LY2949002. Moreover, Sod2 overexpression resulted in increased in vivo blood vessel formation that was H2O2-dependent as assessed by the chicken chorioallantoic membrane assay. Our findings provide the first evidence for the involvement of mitochondrial H2O2 in regulating PTEN function and the angiogenic switch, indicating that Sod2 can serve as an alternative physiological source of the potent signaling molecule, H2O2.


Association between the V109G polymorphism of the p27 gene and the risk and progression of oral squamous cell carcinoma.
Abnormalities in p27 may alter cell cycle delay required for DNA repair after exposure to carcinogens. A coding exon 1 polymorphism at codon 109 (T-->G) in p27 was identified and thought to have an effect on the functions of its protein. We hypothesized that this p27 T109G polymorphism is associated with squamous cell carcinoma of the head and neck (SCCHN) risk. We tested this hypothesis in a hospital-based case-control study of 713 patients newly diagnosed with SCCHN and 1224 cancer-free controls frequency matched to the cases by age (+/-5 years), sex, and smoking status. All subjects were non-Hispanic whites. We genotyped for this p27 variant using genomic DNA from each subject. Compared with the p27 109VV variant, the p27 109GG variant was associated with a nonsignificantly increased risk of SCCHN [crude odds ratio (OR) = 1.29; 95% confidence interval (CI) = 0.88-1.90; adjusted OR = 1.20; 95% CI = 0.81-1.77], but the risk was statistically significant among men (adjusted OR = 1.55, 95% CI = 1.00-2.42), current alcohol users (adjusted OR = 1.68, 95% CI = 1.01-2.82), and patients with oral cavity cancer (adjusted OR = 1.77, 95% CI = 1.03-3.04). The p27 109GG variant was also associated with oral tumor overall stage, suggesting that it may play a role in tumor progression. Our findings suggest that the p27 109GG variant genotype may not play a major role in the etiology of SCCHN but may be associated with an increased risk in at-risk subgroups or subsets of SCCHN, particularly oral cavity cancer and possibly tumor progression. Larger studies with oral squamous cell carcinoma are needed to verify these findings.


Electrical and mechanical modulations by oxygen-derived free-radical generating systems in guinea-pig heart muscles.
The effects of free-radical generating systems and angiotensin-converting enzyme (ACE) inhibitors on the action potentials and contractile force in guinea-pig cardiac muscles were examined using conventional microelectrode and whole-cell voltage-clamp methods at 36 degrees C. Hydrogen peroxide (30-100 microM) prolonged 50%, 75% and 90% repolarization of action-potential duration (APD) approximately 15-25 min after its application. But the longer exposure reversed the APD shortening in a concentration-dependent manner. Other action-potential parameters were not altered to a significant extent. The contractile force was increased. Longer exposure inhibited the enhanced force (but it was still larger than control). The effects on the spontaneous action potential from right atrial muscle were almost the same. In whole-cell voltage-clamp experiments, H2O2 (100 microM) inhibited L-type Ca2+ current and enhanced delayed rectifier K+ current. The effects of light-activated rose bengal (10-100 nM) on the APD were similar to, but more potent than, those of H2O2. The response was observed rapidly after a light illumination. During exposure to rose bengal (100 nM), abnormal spontaneous action potentials or arrhythmias such as a bigeminy occurred, presumably because of early and delayed afterdepolarizations. The responses were irreversible. At 300 microM ACE inhibitors, captopril and enalapril, protected the changes induced by these free radicals. These results indicate that H2O2 has a dual, time-dependent, action on the APD and rose bengal with light illumination produced the responses rapidly. The oxygen-derived free radicals increased [Ca]i and then cellular Ca2+ overload occurred. These responses were protected by ACE inhibitors.


Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer.
To achieve locoregional control of head and neck cancer, survival, and organ preservation using intensive concomitant chemoradiotherapy. This study was a phase II trial of chemoradiotherapy with cisplatin 100 mg/m(2) every 28 days, infusional fluorouracil 800 mg/m(2)/d for 5 days, hydroxyurea 1 g orally every 12 hours for 11 doses, and radiotherapy twice daily at 1.5 Gy/fraction on days 1 through 5 (total dose, 15 Gy). Five days of treatment were followed by 9 days of rest, during which time patients received granulocyte colony-stimulating factor. Five cycles (three with cisplatin) were administered over 10 weeks (total radiotherapy dose, </= 75 Gy). Adjuvant chemoprevention with retinoic acid and interferon alfa-2A was offered. Seventy-six patients were treated (stage IV, 93%; N2, 54%; N3, 21%). At a median follow-up of 38 months, the 3-year progression-free survival is 72%, locoregional control 92%, systemic control 83%, and overall survival 55%. Toxicities included mucositis (grade 3, 45%; grade 4, 12%), neutropenia (grade 4, 39%), and thrombocytopenia (grade 4, 53%). Surgery at the primary site was performed in 13 patients, and 39 had neck dissection. A majority of patients declined adjuvant chemoprevention. Pharmacokinetic parameters were not prognostic of tumor control. Quality of life declined during treatment but returned from good to excellent by 12 months after treatment. Intensive concomitant chemoradiotherapy leads to high locoregional control and survival rates with organ preservation and a reversal of the historical pattern of failure (distant > locoregional). Surgery after concomitant chemoradiotherapy is feasible. Compliance with adjuvant chemoprevention is poor. Identification of less toxic regimens and improved distant disease control emerge as important future research goals.


Utilization of the iOS Shortcuts App to Generate a Surgical Logbook Tool: Feasibility Study.
Surgical audit is an essential aspect of modern reflective surgical practice and is key to improving surgical outcomes. The surgical logbook is an important method of data collection for both personal and unit audits; however, current electronic data collection tools, especially mobile apps, lack the minimum recommended data fields. This feasibility study details the creation of a free, effective surgical logbook tool with the iOS Shortcuts app and investigates the time investment required to maintain a surgical logbook with this tool. In addition, we investigate the potential utility of the Shortcuts app in creating medical data collection tools. Using the iOS Shortcuts app, we created a shortcut "Operation Note," which collects surgical logbook data by using the minimum and extended audit data sets recommended by the Royal Australasian College of Surgeons. We practically assessed the feasibility of the tool, assessing the time requirement for entry, accuracy, and completeness of the entered data. The shortcut collected accurate and useful data for a surgical audit. Data entry took on average 65 seconds per case for the minimum data set, and 135 seconds per case for the extended data set, with a mean difference of 68 seconds (P<.001; 95% CI 61.6-77.7). This feasibility study demonstrates the utility of the iOS Shortcuts app in the creation of a surgical logbook and the time-consuming nature of data collection for surgical audit. Our iOS Operation Note shortcut is a free, rapid, and customizable alternative to currently available logbook apps and offers surgical trainees and consultants a method for recording surgical operations, complications, and demographic data.


Polymorphisms of microsomal epoxide hydrolase gene and severity of HCV-related liver disease.
Factors influencing the progression of liver disease and the development of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV) infection are poorly understood. Inherited variations of drug-metabolizing enzyme (DME) activities may affect liver damage and cancer risk by modifying individual susceptibility to endogenous or exogenous toxic compounds. We investigated the association of liver disease severity with common alleles of microsomal epoxide hydrolase (mEH), an enzyme involved in the metabolism of highly reactive epoxide intermediates. Three polymorphisms (Tyr113His, His139Arg, and -613C/T) were analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphisms (RFLPs) in 394 patients at different stages of disease, including 92 asymptomatic carriers, 109 patients with chronic hepatitis, 100 patients with cirrhosis, and 93 patients with HCC. Reference allele frequencies were obtained from 99 healthy blood donors. Allele distributions between categories were compared using the chi(2) test; odds ratios (ORs) and 95% CI were calculated to express relative risks. Allele frequencies among 99 healthy controls were as follows: 15.1% for 113His/His, 4.0% for 139Arg/Arg, and 46.5% for -613C/T. mEH 113His/His homozygotes were overrepresented in advanced stages of disease, in particular among HCC patients (27.9%; P =.03; OR, 2.2; 95% CI, 1.0-4.6). Differences were more pronounced among men and between extreme patient categories. When mEH genotypes were combined to express a metabolic phenotype, very slow metabolizers were highly prevalent among cirrhotic and HCC patients (18% vs. 3.3% in carriers; P <.001). In conclusion, mEH gene polymorphisms were significantly associated with HCV-related liver disease severity and HCC risk. Men were at higher risk than women; this might be explained by hormonal regulation of gene expression or by differential exposure to environmental toxins.


[The role of color duplex ultrasound in diagnosis and differential diagnosis of carotid body tumors].
Currently the diagnosis of tumorous lesions of the carotid bifurcation is the domain of magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). So far, colour Doppler imaging (CDI) has not been playing an important part in this field. The aim of this study was to define the diagnostic value of CDI in the evaluation of these tumours related to the big arteries and to compare the different imaging techniques. 6 female patients with suspected tumours of the carotid bifurcation were examined with CDI. Additionally 5 MRI examinations and 3 preoperative diagnostic DSA examinations were performed in the same patients. Pathologically, there were 4 typical carotid body tumours, 1 neuroma of the sympathetic trunk and 1 multifocal paraganglioma of the neck. In carotid body tumours we found a characteristic broadening of the bifurcation with shifting of the internal carotid artery posteriorly and laterally and of the external carotid artery anteriorly and medially. The highly vascularized tumour is surrounded by the arteries. This combination of ultrasound findings was absent in cases of sympathetic neuroma and multifocal paraganglioma. No additional information was achieved with MRI and DSA. CDI and MRI evaluation revealed the same diagnostic value in cases of vascularised tumours of the carotid bifurcation. CDI proved to be as accurate as DSA in the imaging of the big arteries and their relationship to the tumour, as well as of the small tumour feeding vessels. Therefore DSA may be omitted as an invasive diagnostic tool in the diagnosis of carotid body tumours.


Definitions of metabolic syndrome: Where are we now?
The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including abdominal obesity, glucose intolerance, hypertension and dyslipidaemia and is associated with an increased risk of vascular events. Since the initial description of the MetS, several expert groups produced different definitions. This variability led to confusion and absence of comparability between studies. Although there is agreement that the MetS is a major public health challenge worldwide and consistent evidence stresses the need for intervention, the definition of the syndrome remains a matter of debate. This review considers the different definitions of the MetS. These include those proposed by the World Health Organisation, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program Adult Treatment Panel III, the American College of Endocrinology and American Association of Clinical Endocrinologists and the latest International Diabetes Federation definition which includes ethnic-specific waist circumference cut-off points. These definitions share several features but also include important differences; all have limitations. Selected (after a Medline search) studies comparing the different definitions are also considered. There is a need for a standardised definition of the MetS. Furthermore, a definition tailored for children and adolescents is essential. Prospective long-term studies are needed to validate the prognostic power of these definitions. As new information becomes available the definition of the MetS might be further modified.


Understanding the connections between climate change, air pollution, and human health in Africa: Insights from a literature review.
Climate change and air pollution are two interconnected global challenges that have profound impacts on human health. In Africa, a continent known for its rich biodiversity and diverse ecosystems, the adverse effects of climate change and air pollution are particularly concerning. This review study examines the implications of air pollution and climate change for human health and well-being in Africa. It explores the intersection of these two factors and their impact on various health outcomes, including cardiovascular disease, respiratory disorders, mental health, and vulnerable populations such as children and the elderly. The study highlights the disproportionate effects of air pollution on vulnerable groups and emphasizes the need for targeted interventions and policies to protect their health. Furthermore, it discusses the role of climate change in exacerbating air pollution and the potential long-term consequences for public health in Africa. The review also addresses the importance of considering temperature and precipitation changes as modifiers of the health effects of air pollution. By synthesizing existing research, this study aims to shed light on complex relationships and highlight the key findings, knowledge gaps, and potential solutions for mitigating the impacts of climate change and air pollution on human health in the region. The insights gained from this review can inform evidence-based policies and interventions to mitigate the adverse effects on human health and promote sustainable development in Africa.


Boosting exercise beliefs and motivation through a psychological intervention designed for poststroke populations.
The effect of patient education on reducing stroke has had mixed effects, raising questions about how to achieve optimal benefit. Because past evaluations have typically lacked an appropriate theoretical base, the design of past research may have missed important effects. This study used a social cognitive framework to identify variables that might change in response to education. A mixed design was used to evaluate 2 approaches to an intervention, both of which included education. Twenty-six seniors completed a measure of stroke knowledge and beliefs twice: before and after an intervention that was either "standard" (educational brochure plus activities that were not about stroke) or "enhanced" (educational brochure plus activities designed to enhance beliefs about stroke). Outcome measures were health beliefs, intention to exercise to reduce stroke, and stroke knowledge. Selected beliefs changed significantly over time but not differentially across conditions. Beliefs that changed were (1) perceived susceptibility to stroke, and (2) perceived benefit of exercise to reduce risk. Benefit beliefs, in particular, were strongly and positively associated with intention to exercise. Findings suggest that basic approaches to patient education may influence health beliefs. More effective stroke prevention programs may result from continued consideration of the role of health beliefs in such programs.


Pupillometry-guided Intraoperative Remifentanil Administration versus Standard Practice Influences Opioid Use: A Randomized Study.
Pupillometry has shown promising results for assessing nociception in anesthetized patients. However, its benefits in clinical practice are not demonstrated. The aim of this prospective randomized study was to evaluate the impact of intraoperative pupillometry monitoring on perioperative opioid consumption in major gynecologic surgery. After receiving ethics committee approval and written consent of patients, American Society of Anesthesiologists status I to II women undergoing gynecologic surgery were included in this single-blinded, prospective, parallel-arm randomized study. General anesthesia was standardized with propofol-remifentanil target-controlled infusion. Patients were randomly assigned into two groups. In the pupillometry group, remifentanil administration was guided by pupillary diameter changes. In the standard group, remifentanil administration was left to the discretion of the anesthesiologist. The primary outcome was intraoperative remifentanil consumption. Fifty-five patients were analyzed. Remifentanil consumption was markedly decreased in the pupillometry group (3.8 [3.4 to 4.8 µg · kg · h] vs. 7.9 µg · kg · h [6.5 to 9.0 µg · kg · h] in the standard group; difference = 4.2 µg · kg · h [95% CI, 3.0 to 5.3 µg · kg · h]; P < 0.001). Cumulative 0- to 12-h morphine consumption was reduced in the pupillometry group (two-way repeated measures ANOVA 0.3 ± 0.1 vs. 0.4 ± 0.2 mg/kg; P = 0.048). A telephone survey 3 months after surgery revealed that 15 of 29 patients in the standard group still experienced procedure-related pain versus 3 of 23 in the pupillometry group (chi-square P = 0.037). No adverse events associated with pupillometry were observed during the study. The use of pupillometry to guide intraoperative analgesia reduced intraoperative remifentanil consumption and postoperative morphine requirements. The possible consequences of decreasing intraoperative remifentanil in terms of chronic pain require further investigation.


Novel enzyme-linked immunosorbent assays for the detection of anti-Fc gamma receptor autoantibodies.
There is a substantial interest in the role of antineutrophil antibodies since Fc gamma receptors (Fc gamma Rs) have been identified as the target for the majority of such autoantibodies. Antineutrophil antibodies have long been detected by an indirect immunofluorescence technique. Following optimization of the flow cytometric method of detection, we developed three enzyme-linked immunosorbent assays (ELISAs), each specific for autoantibodies against one of the three classes of human Fc gamma R. Fc gamma RI and Fc gamma RII were purified from cultured cells, and Fc gamma RIII was produced as a recombinant molecule. These were then used as capture agents in the respective ELISAs. When applied in parallel to a sizeable group of patients with primary Sjögren's syndrome, both methods established that anti-Fc gamma R autoantibodies were heterogeneous. This finding indicates that different populations of partly cross-reactive antibodies are detectable by these two methods.


Experimental investigations on PVA/chitosan and PVA/chitin films for active food packaging using Oxytenanthera abyssinica lignin nanoparticles and its UV-shielding, antimicrobial, and antiradical effects.
This study investigated the effect of adding lignin nanoparticles (LNPs) derived from Oxytenanthera abyssinica via alkali-acid nanoprecipitation method to polyvinyl alcohol/chitosan (PVA/CI) and polyvinyl alcohol/chitin (PVA/CH) films for the active food packaging applications. Adding LNPs at concentrations of 1 % and 3 % improved the films' thermal stability and mechanical properties. The lowest water solubility and moisture content were observed in PVA/CI/LNPs films. LNPs exhibited effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities, with the highest values observed in PVA/CH/LNPS and PVA/CI/LNPS films with values of 87.47 and 88.74 % respectively. The addition of LNPs also improved the UV-blocking abilities of the films. PVA/CH/LNP3 and PVA/CI/LNP3 have the smallest percentage transmission values of 3.34 % and 0.86 % in the UV range. The overall migration of dietary stimulants was lower in PVA/CI/LNPS and PVA/CH/LNPS films compared to PVA film. Antibacterial tests demonstrated the inhibitory capacity of the synthesized biofilms against both gram-positive and negative bacterial species, with the highest inhibitory value of 26 mm. The study suggests that PVA/CH/LNPS and PVA/CI/LNPS films have potential applications as active food packaging materials and can be explored in other potential applications such as drug delivery, tissue engineering, wound healing, and slow-release urea fertilizer development.


Involvement of Pitx2, a homeodomain transcription factor, in hypothyroidism associated reproductive disorders.
Hypothyroid-associated reproductive disorders have now become a striking phenomenon worldwide but the molecular mechanism behind these disorders is not fully known. Pitx2 gene encodes homeodomain transcription factor, which regulates Plod2 gene in brain tissue, transactivates gonadotropin genes in pituitary and plays a substantial role in cell growth and proliferation in different tissues. Pitx2 binds to Plod2 promoter and activates this gene in rat ovary. In this report, we show that Pitx2's expression is markedly reduced in hypothyroid ovary as well as in ovarian granulosa cells, which is recovered with T(3)-supplementation both in vitro and in vivo conditions. Reduced Pitx2 expression could decrease Plod2 expression and hence facilitate ovarian ECM degradation. We have also observed similar pattern of expression of Pitx1 and -3 in hypothyroid and T(3)-supplemented ovaries. The temporal expression of Pitx2 across the estrous cycle shows that it is expressed through all the 4 phases of the cycle and reaches its maximum in the proestrus phase suggesting its possible role in ovulation followed by luteinization. The present study reveals that the reduced Pitx2 expression in hypothyroid ovary could lead to ovarian dysfunction by modulating the Pitx2-Plod2 interaction, further study will be necessary to unravel the complete regulatory mechanism of Pitx2 in ovarian function.


Urological complications following use of recombinant human bone morphogenetic protein-2 in anterior lumbar interbody fusion: presented at the 2012 Joint Spine Section Meeting: clinical article.
The goal of this study was to compare the urological complications in patients after anterior lumbar interbody fusion (ALIF) with and without the use of recombinant human bone morphogenetic protein-2 (rhBMP-2). The authors retrospectively reviewed the medical records of all patients who underwent ALIF with and without rhBMP-2 between January 2002 and August 2010. Patient demographic, operative, and complication information was analyzed. Male patients who underwent ALIF between L-4 and S-1 were contacted to assess postoperative urological complications. Of the 110 male patients who underwent ALIF and were included in this study, 59 were treated with rhBMP-2 and 51 did not receive rhBMP-2. The mean follow-up duration was 17.5 months for the rhBMP-2 group and 30.8 months for the control group. No difference was found regarding the total number of urological complications in the rhBMP-2 group versus the control group (22% vs 20%, respectively; p = 1.0) or for retrograde ejaculation specifically (8% vs 8%, respectively; p = 1.0). In this study, the use of rhBMP-2 with ALIF surgery was not associated with an increased incidence of urological complications and retrograde ejaculation when compared with control ALIF without rhBMP-2. Further prospective analyses that specifically look at these complications are warranted.


What opportunities do European early career psychiatrists have?
In the past century, biological, psychological and social sciences have brought significant progresses to psychiatry, building it is a broad medical specialty, closely linked to somatic medicine, psychology and society. Many psychiatrists early in their career have understood that it is easier to face these challenges in a collaborative way, and therefore there has been in the last decades a growth of local and national associations of psychiatric trainees and early career psychiatrists across Europe. In 2007, the European Psychiatric Association (EPA) has integrated in its program the "Young Psychiatrists Committee", an informal network of young psychiatrists. This Committee since 2010 has been known as the Early Career Psychiatrists Committee (ECPC). EPA has been making remarkable efforts towards supporting early career psychiatrists' education and participation in scientific congresses, promoting their professional growth and integration into the international professional community. Likewise, early career psychiatrists contribute to EPA with their motivation, enthusiasm and creative ideas, proving this initiative as an effective win-win cooperation.


Management of failed prostaglandin abortions.
Midtrimester abortion was induced in 529 patients by administration of the naturally occurring prostaglandins E2 and F2alpha as well as the 15-methyl analogs, 15-ME-PGE2 and 15-ME-PGF2alpha. Ten patients failed to abort with prostaglandin therapy, even in association with intravenous oxytocin, a failure rate of 1.9%. Two failures were related to uterine malformation; 1 patient had the pregnancy in a blind uterine horn, and the second patient was pregnant in one horn of a uterus didelphys. Five of the 10 patients who failed to abort during prostaglandin administration were subsequently found to have uterine distortion due to myomata uteri. When abortion induced by prostaglandin fails to occur within the expected time for the agent and technic employed, the presence of uterine malformation or abnormality should be considered. Evaluation with ultrasonography is indicated along with a repeat test to confirm the pregnancy. If the sonogram is suggestive of uterin malformation, a hysterosalpinogram should be obtained to determine if there is communication between the cervix and the gestational sac. If no communication is present, an intravenous pyelogram should be performed in view of the 90% correlation of urogenital abnormalities, and an exploratory laparotomy should be performed. When a communication exists between the cervix and the gestational sac, the 24 hours of uterine activity induced by the prostaglandin will have resulted in cervical changes so that the cervix can easily be dilated to either a 14 or 16 Hegar dilator and the conceptus can be removed in parts with minimal bleeding.


Governing complex societal problems: The impact of private on public regulation through technological change.
When addressing complex societal problems, public regulation is increasingly complemented by private regulation. Extant literature has provided valuable insights into the effectiveness of such complex governance structures, with most empirical studies focusing on how public regulation influences private regulation. Conversely, the impact of private on public regulation is less well studied. Here, we investigate this impact with a focus on technological change as possible mechanism. Based on a case study of energy efficiency in buildings in Switzerland, we find evidence of a symbiotic interaction between public and private regulation that leads to ratcheting-up of regulatory stringency. We identify technological change as the mechanism linking private and public regulation. We discuss the relevance of our findings for governance literature and regulators.


[Effect of the increasing levels of soil radioactive pollution on the biochemical composition of plants].
The study was undertaken to study a relationship between the changes of some parameters of the biochemical and mineral composition of different plants, such as rape, pods, and lentil, and the levels of soil radiation pollution, by using the conventional methods. Radioactive pollution of dark-grey forest soils was found to cause a change in the biochemical composition of plant seeds even at the level of cesium 137 (137Cs) within the present temporary permissible levels (TPL) (600 Bq/kg): there were elevated concentrations of salts of potassium, phosphorus, ammonia nitrogen, catechols, sucrose, and some amino acids. With the radioactive cesium level exceeding the TPL, biochemical changes in the seeds depended on the species of the plants: in the rape seeds, the additional formation of sucrose and amino acids continued, but less intensively than with its lower radiation; the pod beans were significantly positively correlated with the increasing amounts of catechols.


Provisional materials: key components of interim fixed restorations.
Clinicians have many choices of provisional materials from which to choose when fabricating interim fixed restorations. While traditional materials are still in use today, temporary materials are continuously being updated and improved upon. In addition to the functional necessities required of the provisional material, it must also provide esthetic value for the patient. This article provides an overview of provisional materials, including newer bis-acryls that have helped eliminate some of the challenges associated with traditional acrylic materials. Composite resin preformed crowns for single-unit provisional applications are also discussed, along with CAD/CAM-fabricated materials. Regardless of the material selected, a provisional restoration must maintain and protect the underlying tooth structure from ill effects.


Association between workaholism and sleep problems among hospital nurses.
The present study examined the association between workaholism, the tendency to work excessively hard in a compulsive fashion, and sleep problems among Japanese nurses. A cross-sectional survey was conducted among 600 nurses from 2 university hospitals in Japan using a self-reported questionnaire on workaholism, sleep, job-related variables (i.e., job demands, job control, and worksite support), and demographic variables. A total of 394 nurses returned the questionnaire (response rate=65.7%) and complete data from 312 female nurses were used for analyses (final coverage rate=52.0%). Workaholics, as measured using the Japanese version of the Dutch Workaholism Scale, were defined as those having high scores on both the "work excessively" and "work compulsively" subscales. Logistic regression analyses revealed that workaholics had higher risks for sleep problems in terms of subjective sleep insufficiency, excessive daytime sleepiness at work, difficulty awakening in the morning, and feeling tired when waking up in the morning (odds ratios [OR] of 4.40, 3.18, 3.48, and 4.61, respectively, p<0.05). These remained significant even after adjusting for demographic and job-related variables (OR 3.41, 5.36, 2.56, and 2.77, respectively). However, no significant associations were found between workaholism and insomnia symptoms. These results suggest that workaholic nurses had higher risks for impaired awakening, insufficient sleep, and workplace sleepiness.


Use of a modified ornithine decarboxylase promoter to achieve efficient c-MYC- or N-MYC-regulated protein expression.
One of the advantages of viral-directed enzyme prodrug therapy (VDEPT) is its potential for tumor-specific cytotoxicity. However, the viruses used to deliver cDNAs encoding prodrug-activating enzymes transduce normal cells as well as tumor cells, and several approaches to achieve tumor-specific expression of the delivered cDNAs are being investigated. One such approach is to regulate transcription of the prodrug-activating enzyme with a promoter that is preferentially activated by tumor cells. Published data suggest that the most promising transcription factor/promoter/enhancer combinations are those activated by a tumor-specific transcription factor to retain tumor cell specificity but that are equal in strength to nonspecific viral promoters in their ability to up-regulate target cDNAs. This report identifies MYC-responsive, modified ornithine decarboxylase (ODC) promoter/enhancer sequences that up-regulate target protein expression in tumor cells overexpressing either N-MYC or c-MYC protein. The most efficient of the four constructs assessed contained six additional CACGTG MYC binding sites 5' to the endogenous ODC promoter (R6ODC). Reporter assays with this chimeric promoter/enhancer regulating expression of chloramphenicol acetyltransferase demonstrated 50-250-fold more activity in MYC-expressing cells compared with similar assays with promoterless plasmids. The R6ODC regulatory sequence was approximately equivalent to the CMV promoter in inducing expression of the neomycin resistance gene in c-MYC-expressing SW480 and HT-29 colon carcinoma cells and in N-MYC-expressing NB-1691 neuroblastoma cells. The modified ODC promoter may, therefore, be useful in achieving tissue-specific expression of target proteins in tumor cells that overexpress c- or N-MYC.


Population replacement in Culex fatigans by means of cytoplasmic incompatibility. 2. Field cage experiments with overlapping generations.
Three experiments were carried out in field cages to test the principle of "transport" of a desirable gene or chromosome into a wild Culex fatigans population as a result of the sterility in cross-matings associated with cytoplasmic incompatibility. Cycling populations of Delhi origin were established in the cages and daily releases were made of the IS31B strain, which has Paris cytoplasm and carries a male-linked translocation. It was shown that, if sufficient releases were made to establish a majority of the Paris cytoplasmic type, complete replacement by this cytoplasmic type subsequently occurred. However, as a result of partial compatibility of males of the Delhi population with Paris females, "recombinant" males with Paris cytoplasm and no translocation were produced. In an experiment in which a continuous low rate of "immigration" of a strain of Delhi origin was simulated, a gradual increase of the Paris cytoplasm nontranslocated type occurred, and renewed IS31B releases were necessary after 5 months to restore the predominance of this type. The results are compared with computer predictions and discussed in relation to the transport of genes for filaria refractoriness or chromosome translocations into wild populations.


Conduction velocity along muscle fibers in situ in myasthenia gravis.
The muscle fiber conduction velocity (MFCV) was tested distally in the short head of the biceps brachii muscle in 4 patients with ocular and 16 cases with generalized Myasthenia Gravis. The mean MFCV was decreased in 6 cases with generalized form of the disease, 2 of them with short evolution of the symptoms and without drugs therapy. The overall MFCV of 644 fibers in generalized MG was significantly decreased (p < 0.02) related to the results of controls. The MFCV is an index of the muscle fiber size. Muscle fiber atrophy in MG may be due to functional denervation in patients without drugs therapy or to motor neuropathy caused by drugs or associated with thymoma.


Persistent ectopic pregnancy.
From 1982-1986, 625 tubal ectopic pregnancies were treated at the University of Hawaii School of Medicine Affiliated Hospitals. The percentage of cases in which the involved tube was preserved increased from 7% in 1982 to 26% in 1986. The presence of persistent trophoblastic tissue was diagnosed by elevated serum levels of the beta subunit of human chorionic gonadotropin (beta-hCG) after conservative surgery in four patients. Three of the four patients developed intra-abdominal hemorrhage and required laparotomy. One patient remained asymptomatic despite elevated beta-hCG levels, which disappeared 60 days after surgery. Evaluation of histologic slides demonstrated persistent intraluminal trophoblastic tissue without invasion in two patients, and extraluminal invasion into the tubal wall in one patient. The use of postoperative serial beta-hCG titers might facilitate recognition of this complication in time to prevent further tubal damage and hemorrhage.


High Definition Colonoscopy Combined with i-SCAN Imaging Technology Is Superior in the Detection of Adenomas and Advanced Lesions Compared to High Definition Colonoscopy Alone.
Background. Improved detection of adenomatous polyps using i-SCAN has mixed results in small studies. Utility of i-SCAN as a primary surveillance modality for colorectal cancer screening during colonoscopy is uncertain. Aim. Comparing high definition white light endoscopy (HDWLE) to i-SCAN in their ability to detect adenomas during colonoscopy. Methods. Prospective cohort study of 1936 average risk patients who had a screening colonoscopy at an ambulatory procedure center. Patients underwent colonoscopy with high definition white light endoscopy withdrawal versus i-SCAN withdrawal during endoscopic screening exam. Primary outcome measurement was adenoma detection rate for i-SCAN versus high definition white light endoscopy. Secondary measurements included polyp size, pathology, and morphology. Results. 1007 patients underwent colonoscopy with i-SCAN and 929 with HDWLE. 618 adenomas were detected in the i-SCAN group compared to 402 in the HDWLE group (p < 0.01). More advanced adenomas (≥10 mm) were found by i-SCAN, 79 versus 47 (p = 0.021) and based upon histology alone 37 versus 18 (p = 0.028). Conclusions. i-SCAN detected significantly more adenomas and advanced adenomas compared to high definition white light endoscopy.


Driving improved burns care and patient outcomes through clinical registry data: A review of quality indicators in the Burns Registry of Australia and New Zealand.
In 2009, the Burns Registry of Australia and New Zealand (BRANZ) published a set of clinical quality indicators (QIs) to monitor performance, improve quality of care, and inform and change policy. With several years of data collected since the initial development of the indicators for burns, the BRANZ QI Working Party reviewed the clinical QIs for relevance and meaning, and considered new QIs that had not been collected previously. Using published literature and expert opinion, the QI Working Party, consisting of multidisciplinary burn clinicians, reviewed the QIs for burn care to be included as routine data items in the BRANZ. In July 2016, the list of clinical QIs in the BRANZ was updated to 23 QIs/data items, covering structure, process, and outcome measures. Four QIs were removed as they were not found to be useful, nine QIs/data items were revised, and eight new QIs/data items were added as they were considered to be clinically useful. This review outlines the changes made to the QIs collected by the BRANZ four years since their development and implementation. Ongoing refinement of the BRANZ QIs will ensure that high quality data is collected to drive improvements in clinical and patient outcomes.


Monoclonal antibody to aldolase C: a selective marker for Purkinje cells in the human cerebellum.
A monoclonal antibody to the glycolytic enzyme aldolase C was used in an immunoperoxidase technique on unfixed and formalin-fixed paraffin-embedded tissues from the human central nervous system (CNS) and other tissues. No staining outside the CNS was detected. In the central nervous system the antibody gave a selective and intense staining of Purkinje cell perikarya, axons and dendrites in both fixed and unfixed tissues. In the human fetal brain, positive staining of Purkinje cells was seen from 35-36 weeks' gestation onwards. This coincides with the conversion of Purkinje cells to a tetraploid state, and may reflect increased glycolytic activity accompanying the rapid dendritic growth at this stage of development. Preliminary investigations on a variety of disease states suggest that this antibody may be useful in studies of ischaemic damage, congenital abnormalities and degenerative conditions affecting the cerebellum.


Evaluation of the association between inflammatory markers and the prognosis of Covid-19.
Coronavirus disease 2019 (COVID-19) triggers the immune system and causes changes in the serum level of inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein, ferritin, interleukin-6, LDH, D-dimer, and procalcitonin (PCT); in this study, we investigate the association between the serum level of inflammatory markers and the prognosis of COVID-19, which included mortality and intensive care unit (ICU) admission of patients. This cross-sectional study was conducted on 200 COVID-19 patients hospitalized at Ayatollah Rouhani Hospital, Babol, from March 2020 to March 2021. Demographic indicators and inflammatory markers were recorded in the questionnaire and were investigated based on disease outcome, length of hospitalization, need for non-invasive ventilation (NIV), and need for hospitalization in the ICU and ventilator. Patients who died or were discharged within the first 24 hours of hospitalization (before the test) were excluded from the study. Finally, the data were recorded in SPSS Statistics 26.0 and then analyzed. The average age of patients with COVID-19 hospitalized in the hospital was 57.92 ± 16.18. The prevalence of death due to coronavirus disease in hospitalized patients was 8.5%. Besides, 23.5% of patients were hospitalized in the ICU and 28.5% required NIV. Based on the disease's outcome, a significant difference was found in the neutrophil-to-lymphocyte ratio (NLR), so the NLR was significantly higher in patients who died due to coronavirus. Moreover, the levels of erythrocyte sedimentation rate (ESR), D-dimer, LDH, and PCT in deceased individuals were considerably higher compared to those who recovered. NLR, ESR, D-dimer level, LDH, and PCT are among the markers that affect COVID-19 patient outcomes. The increment of any of these markers will lead to an increase in the risk of death and also the need for ICU admission.


Weaker HLA Footprints on HIV in the Unique and Highly Genetically Admixed Host Population of Mexico.
HIV circumvents HLA class I-restricted CD8+ T-cell responses through selection of escape mutations that leave characteristic mutational "footprints," also known as HLA-associated polymorphisms (HAPs), on HIV sequences at the population level. While many HLA footprints are universal across HIV subtypes and human populations, others can be region specific as a result of the unique immunogenetic background of each host population. Using a published probabilistic phylogenetically informed model, we compared HAPs in HIV Gag and Pol (PR-RT) in 1,612 subtype B-infected, antiretroviral treatment-naive individuals from Mexico and 1,641 individuals from Canada/United States. A total of 252 HLA class I allele subtypes were represented, including 140 observed in both cohorts, 67 unique to Mexico, and 45 unique to Canada/United States. At the predefined statistical threshold of a q value of <0.2, 358 HAPs (201 in Gag, 157 in PR-RT) were identified in Mexico, while 905 (534 in Gag and 371 in PR-RT) were identified in Canada/United States. HAPs identified in Mexico included both canonical HLA-associated escape pathways and novel associations, in particular with HLA alleles enriched in Amerindian and mestizo populations. Remarkably, HLA footprints on HIV in Mexico were not only fewer but also, on average, significantly weaker than those in Canada/United States, although some exceptions were noted. Moreover, exploratory analyses suggested that the weaker HLA footprint on HIV in Mexico may be due, at least in part, to weaker and/or less reproducible HLA-mediated immune pressures on HIV in this population. The implications of these differences for natural and vaccine-induced anti-HIV immunity merit further investigation.IMPORTANCE HLA footprints on HIV identify viral regions under intense and consistent pressure by HLA-restricted immune responses and the common mutational pathways that HIV uses to evade them. In particular, HLA footprints can identify novel immunogenic regions and/or epitopes targeted by understudied HLA alleles; moreover, comparative analyses across immunogenetically distinct populations can illuminate the extent to which HIV immunogenic regions and escape pathways are shared versus population-specific pathways, information which can in turn inform the design of universal or geographically tailored HIV vaccines. We compared HLA-associated footprints on HIV in two immunogenetically distinct North American populations, those of Mexico and Canada/United States. We identify both shared and population-specific pathways of HIV adaptation but also make the surprising observation that HLA footprints on HIV in Mexico overall are fewer and weaker than those in Canada/United States, raising the possibility that HLA-restricted antiviral immune responses in Mexico are weaker, and/or escape pathways somewhat less consistent, than those in other populations.


Impact of a medical home model on costs and utilization among comorbid HIV-positive Medicaid patients.
The Pennsylvania Chronic Care Initiative (CCI) was a statewide patient-centered medical home (PCMH) initiative implemented from 2008 to 2011. This study examined whether the CCI affected utilization and costs for HIV-positive Medicaid patients with both medical and behavioral health comorbidities. Nonrandomized comparison of 302 HIV-positive Medicaid patients treated in 137 CCI practices and 2577 HIV-positive Medicaid patients treated elsewhere. All patients had chronic medical conditions (diabetes, chronic obstructive pulmonary disease, asthma, or congestive heart failure) and a psychiatric and/or substance use disorder. Analyses used Medicaid claims data to examine changes in total per patient costs per month from 1 year prior to 1 year following an index episode. Propensity score weighting was used to adjust for potential sample differences. Secondary outcomes included costs and utilization of emergency department, inpatient, and outpatient/pharmacy services. We identified an average total cost savings of $214.10 per patient per month (P = .002) for the CCI group relative to the non-CCI group. This was a function of decreased inpatient medical (-$415.69; P = .007) and outpatient substance abuse treatment (-$4.86; P = .001) costs, but increased non-HIV pharmacy costs ($158.43; P = .001). Utilization for the CCI group, relative to the non-CCI group, was correspondingly decreased for inpatient medical services (odds ratio [OR], 0.619; P = .002) and inpatient services overall (OR, 0.404; P = .001), but that group had greater numbers of outpatient medical service claims when they occurred (11.7%; P = .003) and increased non-HIV pharmacy claims (9.7%; P = .001). There was increased outpatient service utilization, yet relative cost savings, for HIV-positive Medicaid patients with medical and behavioral health comorbidities who were treated in PCMHs.


[Folic acid: Primary prevention of neural tube defects. Literature Review].
Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.


An extended three-stage treatment to correct a severe skeletal and dental discrepancy.
A report of a case of extended treatment of a patient with severe mandibular retrognathism and an Angle Class II division 1 malocclusion. Initial fixed appliance treatment reduced incisor protrusion. A second phase utilising a Teuscher appliance achieved improved facial and dental relations through excellent mandibular growth. A third phase of fixed Edgewise treatment finalised dental relations.


Three dimensional geometry of acutely ischemic myocardium.
The distribution of coronary flow to small segments of the entire left ventricle (96 per dog; average weight = 0.78 g) was studied in 28 open-chested dogs utilizing 7-10 mu labeled microspheres. Although the flow to large areas of the ventricle was nearly evenly distributed, there was considerable heterogeneity of flow to small adjacent segments of myocardium (average standard deviation of the flow distributions was 17.3 +/- 3.2% of mean lfow). Approximately one-half of the measured heterogeneity of flow could be attributed to various extraneous factors, and one-half appears to be due to inherent heterogeneity of flow in the left ventricular myocardium. In ten of 28 dogs, the mid-circumglex coronary was suddenly occluded, and five minutes thereafter the distribution of left ventricular flow was determined with microspheres labeled with a different isotope. The ischemic regments were separated into three groups: severely ischemic, moderately ischemic, and borderline ischemic. The three dimmensional geometry of the acutely ischemic myocardium was analyzed, and four general conclusions were reached. 1) The percent distribution of severely ischemic segments, moderately ischemic segments, and borderline ischemic segments within an ischemic region varies from animal to animal. 2) Subendocardial segments were more frequently and more severely affected than neighboring mid-wall or epicardial segments. 3) No evidence of an "hyperperfused zone" of myocardium surrounding the ischemic area was found. 4) The flows to segments immediately adjacent to the severely ischemic segments were heterogeneous. Therefore, the concept of a geometrically defined "buffer zone" of moderately ischemic myocardium surrounding and separating severely ischemic from normally perfused myocardium no longer seems realistic.


Severe Complications After Splenic Artery Embolization for Portal Hypertension Due to Hepatic Cirrhosis.
Splenomegaly/hypersplenism is one of the most common complications of portal hypertension. Splenic artery embolization (SAE) has been increasingly used for treatment of splenomegaly/hypersplenism. However, few studies focused on the severe complications after embolization. In this paper, we reported 16 cases of severe complications after SAE for portal hypertension. From February 2011 to January 2019, 16 cirrhotic patients were diagnosed with severe complications after embolization. The clinical symptoms, therapies and prognosis were analyzed. In these patients, the splenic embolization volume was between 50% and 70%. Among 16 cases, 7 patients were diagnosed with splenic abscess and/or left subphrenic abscess, suffered from the insistent fever, and eventually underwent the surgical therapy; 6 patients with left refractory pleural effusion, suffered from severe chest distress, and underwent repeated thoracocentesis or thoracic closed drainage; 3 patients with thrombosis in portal vein needed oral warfarin therapy. In cirrhotic patients, the severe complications after SAE are not uncommon after the procedure. It causes more suffering, prolonged hospital stay and more medical cost in these patients. It was debatable whether this technique was an appropriate technique for portal hypertension due to liver cirrhosis, patients contraindicated for the treatment should be carefully identified to avoid the complications.


Tunable Polyglycerol-Based Redox-Responsive Nanogels for Efficient Cytochrome C Delivery.
The sensitivity of therapeutic proteins is a challenge for their use in biomedical applications, as they are prone to degradation and opsonization, thus limiting their potential. This demands for the development of drug delivery systems shielding proteins and releasing them at the site of action. Here, we describe the synthesis of novel polyglycerol-based redox-responsive nanogels and report on their potential as nanocarrier systems for the delivery of cytochrome C (CC). This system is based on an encapsulation protocol of the therapeutic protein into the polymer network. NGs were formed via inverse nanoprecipitation using inverse electron-demand Diels-Alder cyclizations (iEDDA) between methyl tetrazines and norbornenes. Coprecipitation of CC led to high encapsulation efficiencies. Applying physiological reductive conditions of l-glutathione (GSH) led to degradation of the nanogel network, releasing 80% of the loaded CC within 48 h while maintaining protein functionality. Cytotoxicity measurements revealed high potency of CC-loaded NGs for various cancer cell lines with low IC50 values (up to 30 μg·mL-1), whereas free polymer was well tolerated up to a concentration of 1.50 mg·mL-1. Confocal laser scanning microscopy (CLSM) was used to monitor internalization of free and CC-loaded NGs and demonstrate the protein cargo's release into the cytosol.


[Survey of nursing services with regard to mechanical ventilation at home].
Homecare for mechanically ventilated patients is complex and challenging for homecare institutions. The framework conditions of homecare are regulated by a likewise complex social legislation. The German Respiratory Society (DGP) and the German Interdisciplinary Society for Home Care Ventilation (DIGAB) have published recommendations on the structure of homecare for ventilated patients in their recent guideline and recommended a certification of homecare nursing services. Prior to a certification process, the homecare task force of the DIGAB conducted a survey in order to compare the current structures with the guideline recommendations. Voluntary disclosure of information by means of a written questionnaire consisting of eleven items was requested. 37 homecare institutions with a total of 78 subsidiaries providing service all over Germany returned their questionnaires. While educational standards are mostly in line with the guideline recommendation, it was found that only 43 % of 812 recorded patients followed up with a specialised weaning centre or centre for ventilation. 84 % of these patients were ventilated invasively. In spite of the fact that all homecare institutions took care of invasively ventilated patients, there was a lack of company-owned standards for specific nursing measures. Homecare for ventilated patients in Germany has reached a decent degree of organisation, while follow-up with specialised centres for ventilation, and with that medical specialist care appears to be underserved. The certification process for homecare institutions should be pursued with emphasis in order to create uniform quality standards. The number of invasively ventilated patients in homecare settings is probably higher than previously estimated and could be the result of a lack of weaning capacity.


Artificial intelligence and capsule endoscopy: unravelling the future.
The applicability of artificial intelligence (AI) in gastroenterology is a hot topic because of its disruptive nature. Capsule endoscopy plays an important role in several areas of digestive pathology, namely in the investigation of obscure hemorrhagic lesions and the management of inflammatory bowel disease. Therefore, there is growing interest in the use of AI in capsule endoscopy. Several studies have demonstrated the enormous potential of using convolutional neural networks in various areas of capsule endoscopy. The exponential development of the usefulness of AI in capsule endoscopy requires consideration of its medium- and long-term impact on clinical practice. Indeed, the advent of deep learning in the field of capsule endoscopy, with its evolutionary character, could lead to a paradigm shift in clinical activity in this setting. In this review, we aim to illustrate the state of the art of AI in the field of capsule endoscopy.


Giving advice or making decisions in someone else's place: the influence of impression, defense, and accuracy motivation on the search for new information.
When making decisions, people have been found predominantly to seek information supporting their preferred choice and to neglect conflicting information. In this article, the authors investigate to what extent different types of advisors, who recommend a choice to someone or make a decision on behalf of someone, show the same confirmatory information search. In Experiment 1, the authors presented participants, in the role of advisors, with a client's decision problem and found that when making a recommendation, advisors conducted a more balanced information search than participants who were making a decision for themselves. However, advisors who had to make a decision on behalf of their clients revealed an increased preference for information supporting their position. Experiment 2 suggested that this confirmatory information search was caused by impression motivation: The advisors bolstered their decision to justify it to the client. The results are discussed within the multiple motive framework of the heuristic systematic model.


Impact of Exchange Stay on Alcohol Consumption: Longitudinal Exploration in a Large Sample of European Students.
Each year, more than 300,000 university students take part in European exchange programs. Besides their positive educational and cultural impacts, these programs are also reputed to immerse students in a high-risk festive context where excessive alcohol consumption is strongly present. There is thus a crucial need to evaluate the actual impact of those exchange stays on alcohol consumption. Study abroad (n = 3,950) and local (n = 3,950) European students completed a 2-part longitudinal survey and reported their alcohol consumption before (T1) and during (T2) their exchange stay (or at the beginning of the academic year and 6 months later for local students, constituting the control group). During their exchange stay, individuals studying abroad showed more excessive and harmful alcohol consumption behaviors than local students, as measured by increased general alcohol consumption and binge drinking (BD) scores at T2. In particular, study abroad students under 20 years of age and performing their exchange stay in eastern Europe were the most exposed to excessive alcohol consumption and BD. These results constitute the first large-scale longitudinal confirmation that exchange stays indeed constitute risky contexts in which students significantly increase their consumption and present stronger alcohol-related problems. In view of the rapid and deleterious effects of alcohol consumption in young people, it is essential to promote prevention campaigns targeting this population to limit public health consequences and possible evolution toward severe alcohol use disorders.


Docking for EP4R antagonists active against inflammatory pain.
The lipid prostaglandin E2 (PGE2) mediates inflammatory pain by activating G protein-coupled receptors, including the prostaglandin E2 receptor 4 (EP4R). Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce nociception by inhibiting prostaglandin synthesis, however, the disruption of upstream prostanoid biosynthesis can lead to pleiotropic effects including gastrointestinal bleeding and cardiac complications. In contrast, by acting downstream, EP4R antagonists may act specifically as anti-inflammatory agents and, to date, no selective EP4R antagonists have been approved for human use. In this work, seeking to diversify EP4R antagonist scaffolds, we computationally dock over 400 million compounds against an EP4R crystal structure and experimentally validate 71 highly ranked, de novo synthesized molecules. Further, we show how structure-based optimization of initial docking hits identifies a potent and selective antagonist with 16 nanomolar potency. Finally, we demonstrate favorable pharmacokinetics for the discovered compound as well as anti-allodynic and anti-inflammatory activity in several preclinical pain models in mice.


Determination of a 12 kb nucleotide sequence around the 76 degrees region of the Bacillus subtilis chromosome.
The nucleotide sequence of a 12361 bp DNA segment in the 76 degrees region of the Bacillus subtilis chromosome has been determined. Ten putative ORFs were identified. The deduced amino acid sequences of the products of two of them (glv-1 and glv-2) exhibited high similarity to those of glvG (6-phospho-beta-glucosidase gene) and glvC [permease (the IIC domain) of the phosphotransferase system (PTS)], respectively, in the glv operon of Escherichia coli. The C-terminal region of Glv-2 exhibited similarity to the entire region of GlvB (the IIB domain of PTS) of E. coli, suggesting fusion of the glvC and glvB genes in B. subtilis. glv-1, yfiA and glv-2 seem to form an operon of a phosphoenolpyruvate:sugar PTS, followed by a presumed four-membered operon of an ABC transport system. Moreover, a presumed sugar symporter and its regulatory genes were located in this region.


The diverse roles of peroxisomes in the interplay between viruses and mammalian cells.
Peroxisomes are ubiquitous organelles found in eukaryotic cells that play a critical role in the oxidative metabolism of lipids and detoxification of reactive oxygen species (ROS). Recently, the role of peroxisomes in viral infections has been extensively studied. Although several studies have reported that peroxisomes promote viral replication, evidence indicates that viruses have also evolved diverse strategies to evade peroxisomal antiviral signals. In this review, we summarize the multiple roles of peroxisomes in the interplay between viruses and mammalian cells. Focus is given on the peroxisomal regulation of innate immune response, lipid metabolism, ROS production, and viral regulation of peroxisomal biosynthesis and degradation. Understanding the interactions between peroxisomes and viruses provides novel insights for the development of new antiviral strategies.


Technical Note: Development of a combined molecular breast imaging/ultrasound system for diagnostic evaluation of MBI-detected lesions.
The purpose of this study was to perform a pilot evaluation of an integrated molecular breast imaging/ultrasound (MBI/US) system designed to enable, in real-time, the registration of US to MBI and diagnostic evaluation of breast lesions detected on MBI. The MBI/US system was constructed by modifying an existing dual-head cadmium zinc telluride (CZT)-based MBI gamma camera. The upper MBI detector head was replaced with a mesh panel, which allowed an ultrasound probe to access the breast. An optical tracking system was used to monitor the location of the ultrasound transducer, referenced to the MBI detector. The lesion depth at which ultrasound was targeted was estimated from analysis of previously acquired dual-head MBI datasets. A software tool was developed to project the US field of view onto the current MBI image. Correlation of lesion location between both modalities with real-time MBI/US scanning was confirmed in a breast phantom model and assessed in 12 patients with a breast lesion detected on MBI. Combined MBI/US scanning allowed for registration of lesions detected on US and MBI as validated in phantom experiments. In patient studies, successful registration was achieved in 8 of 12 (67%) patients, with complete registration achieved in seven and partial registration achieved in one patient. In 4 of 12 (37%) patients, lesion registration was not achieved, partially attributed to uncertainty in lesion depth estimates from MBI. The MBI/US system enabled successful registration of US to MBI in over half of patients studied in this pilot evaluation. Future studies are needed to determine if real-time, registered US imaging of MBI-detected lesions may obviate the need to proceed to more expensive procedures such as contrast-enhanced breast MRI for diagnostic workup or biopsy of MBI findings.


Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets.
Rifampin coadministration dramatically reduces plasma lopinavir (LPV) concentrations. In healthy volunteers, doubling the dose of a lopinavir-ritonavir (LPV/r) capsule formulation overcame this interaction, but a subsequent study of double doses of the tablet formulation was stopped early owing to hepatotoxicity. However, healthy-volunteer study findings may not apply to HIV-infected adults. We evaluated the steady-state pharmacokinetics of LPV in HIV-infected adults virologically suppressed on an LPV/r regimen who were given rifampin, and the dose of the LPV/r tablet formulation was gradually increased. The steady-state pharmacokinetics of LPV/r were evaluated at baseline, a week after commencing rifampin, a week after the LPV/r dose was increased 1.5 times, and a week after the LPV/r dose was doubled. Twenty-one participants were enrolled. The median [interquartile range (IQR)] predose LPV concentrations (C(0)) were 8.1 (6.2 to 9.8) mg/liter at baseline, 1.7 (0.3 to 3.0) mg/liter after 7 days of rifampin, 5.9 (2.1 to 9.9) mg/liter with 1.5 times the dose of LPV/r, and 10.8 (7.0 to 13.1) mg/liter with double-dose LPV/r. There were no significant differences in the LPV area under the plasma concentration-time curve from 0 to 12 h (AUC(0-12)), C(0), C(12), maximum concentration of drug in serum (C(max)), or half-life (t(1/2)) between the baseline and double-dose LPV/r time points. Treatment was generally well tolerated, with two participants developing asymptomatic grade 3/4 transaminitis. Doubling the dose of the tablet formulation of LPV/r overcomes induction by rifampin. Less hepatotoxicity occurred in our cohort of HIV-infected participants than was reported in healthy-volunteer studies.


Results of ala carte Posteromedial Soft Tissue Release in Idiopathic Clubfoot.
The aim of this study is to assess the outcomes of ala carte posteromedial release in children over two years of age who were not responding to the Ponseti method of treatment of idiopathic clubfoot. A retrospective observational study from September 2013 to August 2015 was conducted at a tertiary level medical teaching institution. The clubfeet were classified according to the Harold and Walker classification. Radiographic parameters assessed were the talocalcaneal angle (AP, lateral), talus-first metatarsal angle (AP, lateral) and calcaneal-fifth metatarsal angle. The scar and the functional score, according to Laaveg and Ponseti, were evaluated as outcome measures at the final follow-up. Twenty-four children with a mean age of 43.7 ± 24.7 months were enrolled in the study. There was a total of 36 clubfeet: 21 (65.6%) with a poor functional outcome; 12 (37.4%) with excellent to good scar in both horizontal and vertical components. There was a statistical significance between the pre-operative and post-operative radiological parameters (p<0.05). None of the patients presented with any limitation of activities of daily living despite the poor functional outcome in many of the children. There was no significant association between the qualities of scar (horizontal, vertical) and the functional outcome with age at presentation, pre-operative Harold and Walker classification and pre-operative radiographic angles. Surgical intervention in terms of ala carte posteromedial soft tissue release could not produce a good outcome over four years in CTEV. The threshold for surgery in CTEV should be high, given the poor results.


Effects of a flaxseed-derived lignan supplement in type 2 diabetic patients: a randomized, double-blind, cross-over trial.
Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals. The study aimed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control, lipid profiles and insulin sensitivity in type 2 diabetic patients. This was a randomized, double-blind, placebo-controlled, cross-over trial and it was conducted between April and December 2006 in Shanghai, China. Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study. Patients were randomized to supplementation with flaxseed-derived lignan capsules (360 mg lignan per day) or placebo for 12 weeks, separated by an 8-week wash-out period. HbA1c, lipid profiles, insulin resistance index and inflammatory factors were measured. Sixty-eight completed the study and were included in the analyses. The lignan supplement significantly improved glycemic control as measured by HbA(1c) (-0.10+/-0.65 % vs. 0.09+/-0.52 %, P = 0.001) compared to placebo; however, no significant changes were observed in fasting glucose and insulin concentrations, insulin resistance and blood lipid profiles. Urinary excretion of lignan metabolites (enterodiol and enterolactone) was significantly higher after the lignan supplement intervention compared to baseline (14.2+/-18.1 vs. 1.2+/-2.4 microg/mL, P<0.001). Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations. Daily lignan supplementation resulted in modest, yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose, lipid profiles and insulin sensitivity. Further studies are needed to validate these findings and explore the efficacy of lignans on type 2 diabetes. ClinicalTrials.gov NCT00363233.


Health Benefits and Cost-Effectiveness of Asymptomatic Screening for Hypertension and High Cholesterol and Aspirin Counseling for Primary Prevention.
Our aim was to update estimates of the health and economic impact of clinical services recommended for the primary prevention of cardiovascular disease (CVD) for the comparative rankings of the National Commission on Prevention Priorities, and to explore differences in outcomes by sex and race/ethnicity. We used a single, integrated, microsimulation model to generate comparable results for 3 services recommended by the US Preventive Services Task Force: aspirin counseling for the primary prevention of CVD and colorectal cancer, screening and treatment for lipid disorders (usually high cholesterol), and screening and treatment for hypertension. Analyses compare lifetime outcomes from the societal perspective for a US-representative birth cohort of 100,000 persons with and without access to each clinical preventive service. Primary outcomes are health impact, measured by the net difference in lifetime quality-adjusted life years (QALYs), and cost-effectiveness, measured in incremental cost per QALY or cost savings per person in 2012 dollars. Results are also presented for population subgroups defined by sex and race/ethnicity. Health impact is highest for hypertension screening and treatment (15,600 QALYs), but is closely followed by cholesterol screening and treatment (14,300 QALYs). Aspirin counseling has a lower health impact (2,200 QALYs) but is found to be cost saving ($31 saved per person). Cost-effectiveness for cholesterol and hypertension screening and treatment is $33,800 per QALY and $48,500 per QALY, respectively. Findings favor hypertension over cholesterol screening and treatment for women, and opportunities to reduce disease burden across all services are greatest for the non-Hispanic black population. All 3 CVD preventive services continue to rank highly among other recommended preventive services for US adults, but individual priorities can be tailored in practice by taking a patient's demographic characteristics and clinical objectives into account.


Pachydermodactyly treated with tranilast in a young girl.
Introduction. Pachydermodactyly is a rare disease with asymptomatic swelling of proximal interphalangeal joints. This disorder should be considered in the differential diagnosis of juvenile idiopathic arthritis or rheumatoid arthritis. However, pachydermodactyly is not well recognized by many orthopaedic surgeons and rheumatologists. Case Presentation. We report herein a case of a 13-year-old girl with pachydermodactyly. She presented to our clinic with symmetrical swelling of digits II through V without functional loss for the last 4 years. X-ray examination demonstrated no bone or joint destruction and magnetic resonance images showed only thickened skin tissues. No inflammatory signs were seen with laboratory blood tests. We reached a diagnosis of pachydermodactyly by exclusion. We had administered tranilast to her for 6 months and her symptom slightly improved. Conclusion. It is important to recognize pachydermodactyly and be able to differentiate it from other causes of PIP joint swelling such as rheumatoid arthritis, although pachydermodactyly is rare and benign. Physicians including orthopaedists and rheumatologists should make a prompt diagnosis to avoid unnecessary investigations and prevent the patient from receiving inappropriate treatment with steroids or cytotoxic agents. On the other hand, tranilast might be an effective drug to pachydermodactyly.


Errors in the retrieval of thin-cloud optical parameters obtained with a two-boundary algorithm.
The effect of various errors on the retrieval of optical depth, integrated backscatter, and extinction-to-backscatter ratio in optically thin clouds by use of a two-boundary algorithm is discussed. Uncertainties regarding aerosol loading at the cloud base and top lead to relevant errors that are often larger than those produced by signal noise. Formulas expressing the errors in the lidar-derived optical quantities dependent on optical depth and aerosol uncertainties at the base and top are derived for different fitting procedures. A method for the reduction of errors in the case of consecutive cloud measurements is explored, consisting of the fitting of the retrieved optical-depth-integrated backscatter data to obtain a correct extinction-to-backscatter ratio.


Statistical recognition of random and regular phyllotactic patterns.
A statistical method used in ecology is adapted to characterize the degree of order in phyllotactic systems. The test consists of subdividing a planar projection of the stem apical meristem into 16 sectors and counting the number of primordia appearing in each. By dividing the sum of squared deviations by the mean number of primordia per sector the chi-square (chi2) is obtained. When there are a total number of 20 primordia, if the chi2 is less than 6.26, the phyllotaxis is spiral; if it is between 6.26 and 27.5 the phyllotaxis is random; and if it is greater than 27.5, the phyllotaxis is distichous or whorled (level of significance alpha = 5 %). It is also possible to remove one or more sectors. If there are k sectors, the two critical values delimiting the random zone will be found in a chi2 table for k - 1 degrees of freedom. The method is applied to the analysis of sho mutants described by Itoh et al. in 2000 (Plant Cell 12: 2161-2174). The results obtained are in agreement with the theoretical analysis showing that a whorled or spiral phyllotactic system may contain a certain number of randomly distributed elements without losing its regular global structure.


Phenolic profiling in the pulp and peel of nine plantain cultivars (Musa sp.).
The present study investigated the phenolic profiles of the pulp and peel of nine plantain cultivars and compared them to those of two dessert bananas of commercial interest (Grand Nain and Gros Michel), alongside a newly created hybrid, resistant to black sigatoka disease (F568). Identification and quantification of phenolic compounds were performed by means of HPLC-ESI-HR-MS and HPLC-DAD. Hydroxycinnamic acids, particularly ferulic acid-hexoside with 4.4-85.1 μg/g of dry weight, dominated in the plantain pulp and showed a large diversity among cultivars. Flavonol glycosides were predominant in plantain peels, rutin (242.2-618.7 μg/g of dry weight) being the most abundant. A principal component analysis on the whole data revealed that the phenolic profiles of the hybrid, the dessert bananas and the pure plantains differed from each other. Plantain pulps and peels appeared as good sources of phenolics, which could be involved in the health benefits associated with their current applications.


Usefulness of Inflammation-Based Prognostic Scores for Predicting the Risk of Complications After Radical Resection of Colorectal Carcinoma.
We aimed to investigate the value of inflammation-based prognostic scores for predicting early complications after radical surgery for colorectal carcinoma. We retrospectively analyzed data of 154 patients who underwent elective resection of colorectal carcinoma between January 2017 and December 2018 at Beijing Friendship Hospital. Univariate, multivariate, and receiver operating characteristic curve analyses were conducted. As inflammation indices, we evaluated the preoperative modified Glasgow Prognostic Score (GPS), as well as the C-reactive protein/albumin ratio (CAR), postoperative GPS, and C-reactive protein levels on postoperative day 3 (POD3). Within 30 days postoperatively, complications occurred in 80 patients (51.9%). And high levels of preoperative mGPS (P=0.002), preoperative CAR (P=0.019), POD3 CAR (P<0.001) and POD3 poGPS (P<0.001) can significantly affect postoperative complications after surgery for colorectal cancer, with CRP on POD3 (odds ratio, 1.015; 95% confidence interval, 1.006-1.024; P=0.001) as independent risk factors. Among all inflammation-based indicators, POD3 CAR had the highest area under the curve (0.711) and positive predictive value (83.2%). Higher CAR (≥2.6) on POD3 was associated with a higher rate of complications (92.9% vs 36.6%, P<0.001), especially of infectious nature (54.8% vs 16.1%, P<0.001). CAR≥2.6 on POD3 reflects sustained systemic inflammation and represents a useful predictor of complications after surgery for colorectal carcinoma, facilitating early detection, timely intervention, and enhanced recovery.


How bacterial pathogens colonize their hosts and invade deeper tissues.
Bacterial pathogens have evolved a wide range of strategies to colonize and invade human organs, despite the presence of multiple host defense mechanisms. In this review, we will describe how pathogenic bacteria can adhere and multiply at the surface of host cells, how some bacteria can enter and proliferate inside these cells, and finally how pathogens may cross epithelial or endothelial host barriers and get access to internal tissues, leading to severe diseases in humans.


Palmitoylethanolamide increases after focal cerebral ischemia and potentiates microglial cell motility.
Focal cerebral ischemia (FCI) induces rapid neuronal death in the ischemic core, which gradually expands toward the penumbra, partly as the result of a neuroinflammatory response. It is known that propagation of neuroinflammation involves microglial cells, the resident macrophages of the brain, which are highly motile when activated by specific signals. However, the signals that increase microglial cell motility in response to FCI remain mostly elusive. Here, we tested the hypothesis that endocannabinoids mediate neuroinflammation propagation by increasing microglial cell motility. We found that, in mouse cerebral cortex, FCI greatly increases palmitoylethanolamide (PEA), only moderately increases anandamide [arachidonylethanolamide (AEA)], and does not affect 2-arachidonoylglycerol levels. We also found that PEA potentiates AEA-induced microglial cell migration, without affecting other steps of microglial activation, such as proliferation, particle engulfment, and nitric oxide production. This potentiation of microglial cell migration by PEA involves reduction in cAMP levels. In line with this, we provide evidence that PEA acts through Gi/o-coupled receptors. Interestingly, these receptors engaged by PEA are pharmacologically distinct from CB1 and CB2 cannabinoid receptors, as well as from the WIN and abn-CBD (abnormal-cannabidiol) receptors, two recently identified cannabinoid receptors. Our results show that PEA and AEA increase after FCI and synergistically enhance microglial cell motility. Because such a response could participate in the propagation of the FCI-induced neuroinflammation within the CNS, and because PEA is likely to act through its own receptor, a better understanding of the receptor engaged by PEA may help guide the search for improved therapies against neuroinflammation.


Surgical therapy of the thyroid papillary carcinoma in children: experience with 56 patients < or =16 years old.
This article is an anatomic, clinical, therapeutic, and prognostic assessment of 56 children 16 years of age or younger, who underwent a surgical operation for thyroid papillary carcinoma from April 1988 to December 2001 in the Department of General Surgery at the University of Pisa. Of these 56 patients, 22 are Belarus children (39%) in whom carcinoma developed after the nuclear accident in Chernobyl in April 1986, whereas 34 (61%) are children with differentiated nonirradiated tumors. The purpose of this work was to compare the group of children who had radiation-induced thyroid carcinoma with the group affected by non-radiation-induced carcinoma to evaluate if there are significant clinical, anatomic, and prognostic differences between them and to identify the best surgical strategy to adopt. At the time of clinical presentation, the tumor was limited to the thyroid gland in 28 cases (50%), whereas in the others, in 24 cases (43%) metastases in the neck lymph nodes were present or had infiltrated the extrathyroid tissues as was seen in 4 cases (7%). The surgical operation was a total thyroidectomy in 37 cases (66%), whereas in 19 patients with radiation-induced carcinoma it was a hemithyroidectomy followed by a completion of thyroidectomy in Pisa (34%). The histologic examination showed multifocal sites of papillary adenocarcinoma in the gland in 23% of cases, and both lobes of the thyroid gland were involved with tumor in 23% of patients. The postsurgical follow-up showed a mortality rate of 0% and a recurrence rate of 33.5% (64% radiation-induced carcinoma v 3% non-radiation-induced carcinoma; P < .0001). At the moment, 8 of 22 cases (36%) with radiation-induced carcinoma are free of disease versus 33 of 34 (97%) with non-radiation-induced carcinoma (P < .0001). These findings show carcinoma of the thyroid in children has a low risk of mortality but a high risk of recurrence. Children with radiation-induced thyroid carcinoma are more likely to have a recurrence of the disease. Total thyroidectomy for the treatment of both radiation-induced and non-radiation-induced carcinomas appears to represent, on the basis of these results, the best therapeutic option.


External-beam radiation therapy for clinically localized prostate cancer: patterns of care studies in the United States.
Data are presented from the Patterns of Care Study and other sources that define the role of external-beam irradiation in the management of localized prostate cancer as practiced in the United States as a whole. Patients must be treated with complex treatment techniques and high-energy linear accelerators and careful adjustment of radiation dose. Transurethral resection of the prostate should be avoided in the intermediate and poorly differentiated subgroup of stage C patients. The excellent 5- and 10-year survival for patients treated by radiation therapy is demonstrated for all stages of prostate cancer and for T1 or early stage B patients. It is noted that the national averages for survival have improved between 1973 and 1978. Stages A2 and B patients with negative lymph node dissections show freedom from recurrence that is equal to patient reports for radical surgery. Complications resulting from radiation therapy were modest, and potency was maintained in 73% of the patients. Adjuvant irradiation is necessary for pathologic stage C patients after recovery from surgery. Radiation therapy is equally effective though less costly than surgery for early prostate cancer. A particular need of future research is the study of the patterns of care in the United States regarding the surgical management of prostate cancer so that health professionals can determine if this care is generally available throughout the United States and if good outcome and acceptable morbidity result after it is given.


Physiological control of energy balance.
Physiological control of energy balance is reviewed in terms of food seeking and enery (food) intake, utilization and storage. In particular the role of hormonal and metabolic signals, as clarified by whole-body calorimetry and cellular studies, and the interaction of energy expenditure with the mechanism regulating intake are outlined.


Correlation between Deep Venous Thrombosis and Inflammation in Patients after Implantation of Permanent Pacemaker.
The correlation between postoperative deep venous thrombosis (DVT) and inflammation in patients with permanent cardiac pacemaker implantation was analyzed. A total of 130 cases undergoing permanent pacemaker implantation in the 305 Hospital of Chinese PLA and Fuwai Hospital from May 2014 to February 2017 were selected. Of the 130 cases, 60 patients complicated with DVT were selected as the observation group, and the remaining 70 cases without complications of DVT were selected as the control group. The relationship and influence of various factors were explored. The number of patients smoking and the number of subjects with DVT history in the observation group were higher than those in the control group. In the observation group, plasminogen activator inhibitor (PAI)-1: Ag, PAI-1: Ac, thrombin-activated fibrinolysis inhibitor (TAFI): Ag, and TAFI: Ac levels were higher than those in control group (P<0.05). The levels of inflammatory factors of the peripheral blood of the observation group were significantly higher than those of the control group (P<0.05). In the correlation analysis of serum inflammatory factors and coagulation factors, CRP, IL-6, IL-10 were positively correlated with PAI-1: Ag level. Age, BMI, smoking history, number of implanted electrodes, DVT history, duration of immobilization and inflammatory factor levels had independent predictive value on postoperative complicated DVT. The serum inflammatory factors are closely associated with postoperative DVT in patients implanted with permanent cardiac pacemaker, and the serum inflammatory factors are a good reference for the evaluation of DVT.


Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro.
Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), which has been shown to be a clinically effective treatment for erectile dysfunction. Its action results from increased levels of cyclic guanosine monophosphate (cGMP), which is normally degraded by PDE5. This cyclic nucleotide is a second messenger for nitric oxide, which is involved in the regulation of numerous functions, including vascular smooth muscle tone. In an attempt to better predict the effects of sildenafil on cardiovascular function, the distribution of PDE activity was determined with anti-PDE1 and anti-PDE5 antibodies in the human cardiac ventricle and saphenous vein, and in vitro studies were performed on the isolated human cardiac ventricle, corpus cavernosum, saphenous vein, and mesenteric artery as well as on rabbit aorta, dog coronary artery, dog trabecular tissue, and rabbit and human platelets. The major PDE activity in the human cardiac ventricle was shown to be calcium/calmodulin-dependent PDE1, but there was no detectable level of PDE5. In contrast, the human saphenous vein contained PDEs 1, 4, and 5, and the human mesenteric artery contained PDEs 1, 2, 3, 4, and 5. The distribution of PDE5 in the cardiovascular system is consistent with the observed pharmacodynamic and clinical effects of sildenafil. Sildenafil, unlike milrinone, a selective PDE3 inhibitor, had no effect on the isolated trabeculae carneae; this is consistent with the lack of PDE5 expression in cardiac myocytes. Sildenafil selectively increased cGMP levels in coronary vascular smooth muscle tissue but produced no change in cyclic adenosine monophosphate (cAMP) levels, which is consistent with the drug's selectivity for PDE5. In phenylephrine-contracted isolated rabbit aortic rings, sildenafil enhanced the relaxation induced by the nitric oxide donor glyceryl trinitrate, suggesting that sildenafil may potentiate the hypotensive effects of nitric oxide donor agents on the vasculature, an effect that has been observed clinically. Human platelets were found to contain PDE5, which was inhibited by 50% (IC50) by sildenafil at a concentration of 6.3 nM, consistent with the IC50 value in the corpus cavernosum. Sildenafil alone had no direct effect on platelet function, but it potentiated the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human platelets. The pharmacodynamic and adverse event profiles observed in clinical trials with sildenafil are consistent with the in vitro profile of the tissue distribution of PDE5 and its known mechanism of action as a selective inhibitor of PDE5.


Current Insights and Latest Updates in Sperm Motility and Associated Applications in Assisted Reproduction.
Spermatozoon is a motile cell with a special ability to travel through the woman's reproductive tract and fertilize an oocyte. To reach and penetrate the oocyte, spermatozoa should possess progressive motility. Therefore, motility is an important parameter during both natural and assisted conception. The global trend of progressive reduction in the number and motility of healthy spermatozoa in the ejaculate is associated with increased risk of infertility. Therefore, developing approaches for maintaining or enhancing human sperm motility has been an important area of investigation. In this review we discuss the physiology of sperm, molecular pathways regulating sperm motility, risk factors affecting sperm motility, and the role of sperm motility in fertility outcomes. In addition, we discuss various pharmacological agents and biomolecules that can enhance sperm motility in vitro and in vivo conditions to improve assisted reproductive technology (ART) outcomes. This article opens dialogs to help toxicologists, clinicians, andrologists, and embryologists in understanding the mechanism of factors influencing sperm motility and various management strategies to improve treatment outcomes.